Source:http://linkedlifedata.com/resource/pubmed/id/16682954
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
44
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pubmed:dateCreated |
2006-9-28
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pubmed:abstractText |
An inverse relationship exists between the expression of 15-lipoxygenase-2 (15-LOX-2) and peroxisome proliferator-activated receptor gamma (PPARgamma) in normal prostate epithelial cells (PrECs) compared with their expression in prostate carcinoma cells (PC-3). The reason for this difference, however, is unknown. We hypothesized that this inverse expression partly involves the 15-LOX-2 promoter and 15-S-hydroxyeicosatetraenoic acid (15-(S)-HETE), a product of 15-LOX-2 that binds to PPARgamma. We identified an active steroid nuclear receptor half-site present in the 15-LOX-2 promoter fragment F-5 (-618/+177) that can interact with PPARgamma. After forced expression of wild-type PPARgamma, 15-(S)-HETE (1 microM) decreased F-5 reporter activity in PrECs whereas forced expression of 15-LOX-2 resulted in 15-(S)-HETE production which enhanced F-5 activity in PC-3. In contrast, the expression of dominant-negative PPARgamma reversed the transcriptional activation of F-5 by enhancing it 202-fold in PrEC or suppressing it in PC-3; the effect in PC-3 was positively increased 150-fold in the presence of 15-(S)-HETE (1 microM). Peroxisome proliferator-activated receptor gamma interacted with 15-LOX-2 promoter sequences in pulldown experiments using biotinylated 15-LOX-2 (-560/-596 bp) oligonucleotides. In gelshift analyses PPARgamma and orphan receptor RORalpha were shown to interact with the F-5 fragment in PC-3 cells. These data suggest that crosstalk mechanisms exist between the 15-LOX-2 gene and PPARgamma to counterbalance expression and help explain the inverse relationship of these genes in normal versus cancer cells.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/15-hydroxy-5,8,11,13-eicosatetraenoi...,
http://linkedlifedata.com/resource/pubmed/chemical/5' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonate 15-Lipoxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyeicosatetraenoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoxygenase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0950-9232
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pubmed:author |
pubmed-author:DryP JPJ,
pubmed-author:KitSS,
pubmed-author:KriegPP,
pubmed-author:LippmanS MSM,
pubmed-author:LlansaNN,
pubmed-author:LogothetisC JCJ,
pubmed-author:MendozaGG,
pubmed-author:MenterD GDG,
pubmed-author:NewmanR ARA,
pubmed-author:SabichiA LAL,
pubmed-author:SubbarayanVV,
pubmed-author:YangPP
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pubmed:issnType |
Print
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pubmed:day |
28
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6015-25
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:16682954-5' Untranslated Regions,
pubmed-meshheading:16682954-Arachidonate 15-Lipoxygenase,
pubmed-meshheading:16682954-Cell Line,
pubmed-meshheading:16682954-Cell Line, Tumor,
pubmed-meshheading:16682954-Chromosomes, Human, Pair 17,
pubmed-meshheading:16682954-Cloning, Molecular,
pubmed-meshheading:16682954-Down-Regulation,
pubmed-meshheading:16682954-Enhancer Elements, Genetic,
pubmed-meshheading:16682954-Feedback, Physiological,
pubmed-meshheading:16682954-Humans,
pubmed-meshheading:16682954-Hydroxyeicosatetraenoic Acids,
pubmed-meshheading:16682954-Lipoxygenase Inhibitors,
pubmed-meshheading:16682954-Male,
pubmed-meshheading:16682954-PPAR gamma,
pubmed-meshheading:16682954-Promoter Regions, Genetic,
pubmed-meshheading:16682954-Prostate,
pubmed-meshheading:16682954-Prostatic Neoplasms,
pubmed-meshheading:16682954-Receptor Cross-Talk,
pubmed-meshheading:16682954-Up-Regulation
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pubmed:year |
2006
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pubmed:articleTitle |
15-Lipoxygenase-2 gene regulation by its product 15-(S)-hydroxyeicosatetraenoic acid through a negative feedback mechanism that involves peroxisome proliferator-activated receptor gamma.
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pubmed:affiliation |
Department of Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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